Taking notice of high coordinative ability to metal atoms, various hydroxamic acid compounds have been developed as a metalloenzyme inhibitor. Although peptide-based compounds have mostly been developed (see, for example, WO94/02447 and WO90/05719), various compounds containing sulfonic acid amide in a partial structure have recently been published and, for example, European Patent Publication (EP1081137) discloses a compound having the same N-sulfonylpiperidine-2-hydroxamic acid structure as that of the compound of the present invention as an aggrecan degrading enzyme inhibitor.
For a metalloenzyme as a target of inhibition, for example, MMP (WO90/05716) such as collagenases, stromelysins and gelatinases, TNF-α producing enzyme (WO 94/10990) and Fas ligand solubilization enzyme (WO 97/09066) have become of major interest in view of the development of medicaments.
It is known that EGF family growth factors are syntheszied as membrane-bound proteins as precursors which are broken into a soluble form by action of the metalloenzyme, and thus the resulting soluble ligand binds to EGF receptors. In case of HB-EGF among them, the solubilization process plays an important role in the proliferation of keratinocytes (WO 01/70269). Said publication discloses that a hydroxamic acid derivative having a tetrahydroisoquinoline skeleton inhibits a solubilizing enzyme of HB-EGF and is useful as a remedy for keratinocyte-proliferative diseases.